Piezo1 deletion ameliorates inflammation and functional recovery in spinal cord injury through altering microglia/macrophage phenotype

Disruption of their homeostasis post-spinal cord injury (SCI) triggers severe secondary inflammation. This study focuses on Piezo1, a key mediator of macrophage/microglia-driven neuroinflammation. We aimed to promulgate the effect of deleting or inhibiting macrophage/microglial Piezo1 on the neural function after SCI in vitro and vivo. Here, we used C57BL/6J mice in which Piezo1 was specifically deleted in macrophages/microglia (Piezo1-CKO, Piezo1 [flox/flox, Cx3cr1-Cre]). We investigated the expression dynamics of Piezo1 following SCI, explored the phenotypic switching of macrophages/microglia under inflammatory cytokine stimulation, and examined the changes in hindlimb motor function in Piezo1-deficient mice. Our data demonstrated that macrophages/microglia in the injured segment gathered and activated after SCI, and the number of Pierzo1 + macrophages/microglia reached the peak at the 7th day. Piezo1 leads to pro-inflammatory response of macrophages/microglia with IFNγ/LPS stimulation, while inhibition of Piezo1 can lead to anti-inflammation under IL4/IL13 stimulation. Subsequently, Piezo1-CKO mice exhibited a faster and better recovery of neural function after SCI. These findings suggested that Piezo1 deletion ameliorates inflammation and functional recovery in spinal cord injury through altering microglia/macrophage phenotype.